Gloucester back Josh Hathaway will make his Test debut and Cardiff’s Ben Thomas has been handed the fly-half role when Wales face Australia in Sydney on Saturday.
Aberystwyth-born Hathaway, who has represented Wales and England at under-20 level, starts on the wing.
Wales head coach Warren Gatland moved quickly to secure the 20-year-old’s services, which was brought into sharp focus after Exeter wing Immanuel Feyi-Waboso was in a similar position last season and chose England.
“We want to make sure we qualify him for Wales,” Gatland said, after naming his training squad in June.
“He is a young player with a lot of potential and we think there is a lot of improvement in his game, whether it is wing or full-back.”
A reshuffled back-three from the team beaten by world champions South Africa at Twickenham sees Liam Williams move from wing to full-back, with Cameron Winnett dropping out after starting Wales’ last six Tests.
Thomas, meanwhile, makes his first international appearance since 2021 after being preferred to Sam Costelow in the number 10 shirt.
He will have some familiar faces alongside him, though, with Cardiff colleagues Ellis Bevan and Mason Grady starting at scrum-half and inside centre, respectively.
Elsewhere, there is a first Test start for Sydney-born Bath prop Archie Griffin, while Exeter forwards Christ Tshiunza and Dafydd Jenkins join forces in the second-row and number eight Aaron Wainwright wins his 50th cap.
Williams, Wainwright and prop Gareth Thomas are the only starting line-up survivors from Wales’ record 40-6 victory over Australia at the 2023 World Cup.
And Wales face a tough task against the Wallabies, having not beaten them Down Under since 1969, losing 11 successive games.
Gatland said: “We have had a good week of preparations here in Sydney, and are excited to get out on the field on Saturday.
“This first Test is going to be a great challenge for us.
“Test matches are all about fine margins and we know we need to be accurate, keep our discipline and stay in the fight for the full 80 minutes.
“There is a lot of talent within the Australia squad and we know they will want to come out firing and put in a performance against us.”
Former Ireland boss Joe Schmidt takes charge of Australia for the first time after succeeding Eddie Jones as head coach.
Schmidt has named a new-look team, appointing flanker Liam Wright as captain, with uncapped centre Josh Flook and lock Jeremy Williams also selected.
And there are five newcomers among the replacements, including Tom Lynagh, who is the son of Wallabies World Cup winner Michael Lynagh and brother of Italy international Louis Lynagh.
Wales team: L Williams (Kubota Spears); J Hathaway (Gloucester), O Watkin (Ospreys), M Grady (Cardiff), R Dyer (Dragons); B Thomas (Cardiff), E Bevan (Cardiff); G Thomas (Ospreys), D Lake (Ospreys, capt), A Griffin (Bath), C Tshiunza (Exeter), D Jenkins (Exeter), T Plumtree (Scarlets), T Reffell (Leicester), A Wainwright (Dragons).
Replacements: E Lloyd (Cardiff), K Mathias (Scarlets), H O’Connor (Scarlets), C Hill (Secom Rugguts), J Botham (Cardiff), K Hardy (Ospreys), S Costelow (Scarlets), N Tompkins (Saracens).